Contrast agent to assess quality of occlusion through impedance measurement

ABSTRACT

A method, system, and device for predicting lesion quality. Specifically, lesion quality may be predicted based on an assessment of pulmonary vein occlusion using injection of an impedance-modifying agent and evaluation of changes in impedance measurements recorded by an electrode located distal to an occlusion element of the treatment device used to inject the impedance-modifying agent. The quality of the occlusion may be rated based on the changes in impedance over time within the pulmonary vein. For example, the quality of the occlusion may be rated as being good, fair, or poor. This assessment may be quickly and easily communicated to an operator.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 14/689,180, filed Apr. 17, 2015, entitled CONTRASTAGENT TO ASSESS QUALITY OF OCCLUSION THROUGH IMPEDANCE MEASUREMENT, nowissued U.S. Pat. No. 9,956,025, which application is related to andclaims priority to U.S. Provisional Patent Application Ser. No.62/088,267, filed Dec. 5, 2014, entitled USE OF COLD SALINE TO REPLACEDYE IN DETERMINING CRYO BALLOON PV OCCLUSION, the entirety of both ofwhich are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

n/a

FIELD OF THE INVENTION

The present Application relates to a method, system, and device forpredicting lesion quality and other interventions requiring vascularocclusion. Specifically, lesion quality may be predicted based on anassessment of pulmonary vein occlusion using an injectedimpedance-modifying agent. This assessment may be quickly and easilycommunicated to an operator.

BACKGROUND OF THE INVENTION

Cardiac arrhythmia is a condition in which the heart's normal rhythm isdisrupted. Certain types of cardiac arrhythmias, including ventriculartachycardia and atrial fibrillation, may be treated by ablation (forexample, radiofrequency (RF) ablation, cryoablation, ultrasoundablation, laser ablation, microwave ablation, and the like), eitherendocardially or epicardially.

Procedures such as pulmonary vein isolation (PVI) are commonly used totreat atrial fibrillation. This procedure generally involves the use ofa cryogenic device, such as a catheter, which is positioned at theostium of a pulmonary vein (PV) such that any blood flow exiting the PVinto the left atrium (LA) is completely blocked. Once in position, thecryogenic device may be activated for a sufficient duration to create adesired lesion within myocardial tissue at the PV-LA junction, such as aPV ostium. If a cryoballoon is used as the treatment element of thecryogenic device, the balloon is typically inflated using a fluidcoolant, enabling the balloon to create a circumferential lesion aboutthe ostium and/or antrum of the PV to disrupt aberrant electricalsignals exiting the PV.

The success of this procedure depends largely on the quality of thelesion(s) created during the procedure. Currently known methods forevaluating lesion quality may include monitoring the temperature withinthe cryoballoon, but this method can be inaccurate. The success of a PVIprocedure also depends on whether the cryoballoon has completelyoccluded the PV. For example, a complete circumferential lesion isproduced only when the cryoballoon has completely occluded the PV.Incomplete occlusion allows blood to flow from the PV being treated,past the cryoballoon, and into the left atrium of the heart. This flowof warm blood may prevent the cryoballoon from reaching temperatures lowenough to create permanent lesions in the target tissue, or could leavegaps of non-ablated tissue at regions where blood leaks past theballoon. The creation of reversible lesions may not be sufficient toachieve electrical isolation and, as a result, atrial fibrillation maybe likely to reoccur. Additionally, even if the PV is completelyoccluded, suboptimal operation of the cryoablation system may result incryoballoon temperatures that are not low enough, or not applied for asufficient amount of time, to create permanent lesions in the targettissue.

Current methods of assessing or monitoring PV occlusion may includemonitoring changes in impedance measurements of blood and tissue.Although these methods may be effective, changes in recorded impedancecaused by incomplete PV occlusion may be small and could be difficult todetect when trying to quantify the importance of the blood leak aroundthe balloon. Both blood and tissue conduct electricity well and thedistinction between their respective conductivities is small.

It is therefore desirable to provide a cryoablation method, system, anddevice that allows for real-time and accurate assessment of PV occlusionbefore a PV ablation procedure based on recorded impedance measurements.It is also desirable to provide for a method, system, and device thatallow for the communication of PV occlusion assessment to the operatorquickly and easily.

SUMMARY OF THE INVENTION

A method, system, and device for predicting lesion quality.Specifically, lesion quality may be predicted based on an assessment ofpulmonary vein occlusion using injection of an impedance-modifying agentand evaluation of changes in impedance measurements recorded by anelectrode located distal to an occlusion element of the treatment deviceused to inject the impedance-modifying agent. The quality of theocclusion may be rated based on the changes in impedance over timewithin the pulmonary vein

A system for assessing occlusion may include a treatment deviceincluding an occlusion element and an electrode distal to the occlusionelement a console including a fluid source in fluid communication withthe treatment device, the fluid being a mixture of a contrast medium andan impedance-modifying agent and a processor programmed to receiveimpedance values recorded by the electrode, to calculate a change in theimpedance values over time, and to determine an occlusion status basedon the change in the impedance data. The processor may further beprogrammed to predict the quality of a lesion created in tissue by theocclusion element based on the occlusion status determination. Forexample, a determination that the pulmonary vein is partially occludedmay include at least one of assigning the occlusion by the processor apoor rating and assigning the occlusion a fair rating and adetermination that the pulmonary vein is completely occluded includesassigning the occlusion by the processor a good rating. Further,occlusion may be assigned a good rating when the change in impedancevalues has a first value, occlusion may be assigned a fair rating whenthe change in impedance values has a second value, and occlusion may beassigned a poor rating when the change in impedance values has a thirdvalue, the first value being less than each of the second value and thethird value. The occlusion element may be a balloon. The device mayfurther include a thermocouple located within the balloon. The treatmentdevice may further include a shaft having a central lumen and a distalopening, the shaft being at least partially disposed within the balloon,the central lumen and distal opening being in fluid communication withthe fluid source. The mixture of the contrast medium and theimpedance-modifying agent may be injected from the treatment device intoa pulmonary vein. The impedance-modifying agent may increase theimpedance of fluid within the pulmonary vein. For example, the processormay be programmed to determine the occlusion status is poor when theimpedance values recorded by the electrode initially increase and thendecrease over time and/or may be programmed to determine the occlusionstatus is good when the impedance values recorded by the electrodeinitially increase and then plateau. Alternatively, theimpedance-modifying agent may decrease the impedance of fluid within thepulmonary vein. For example, the processor may be programmed todetermine the occlusion status is poor when the impedance valuesrecorded by the electrode initially decrease and then increase over timeand/or may be programmed to determine the occlusion status is good whenthe impedance values recorded by the electrode initially decrease andthen plateau.

A system for predicting lesion quality may include a treatment deviceincluding an occlusion element and an electrode distal to the occlusionelement, the treatment device injecting an impedance-modifying agentinto a pulmonary vein and a processor in communication with andreceiving impedance data from the electrode, the processor programmedto: calculate a rate of impedance change over time after theimpedance-modifying agent is injected into the pulmonary vein; determinea pulmonary vein occlusion status based at least in part on the rate ofimpedance change; and predict a lesion quality, the lesion quality beingbased at least in part on the pulmonary vein occlusion status. Theimpedance-modifying agent may increase impedance of a fluid within thepulmonary vein. For example, the processor may be programmed todetermine the occlusion status is poor when the impedance valuesrecorded by the electrode initially increase and then decrease overtime, and the processor may be programmed to determine the occlusionstatus is good when the impedance values recorded by the electrodeinitially increase and then plateau. Alternatively, theimpedance-modifying agent may decrease impedance of a fluid within thepulmonary vein. For example, the processor may be programmed todetermine the occlusion status is poor when the impedance valuesrecorded by the electrode initially decrease and then increase overtime, and the processor may be programmed to determine the occlusionstatus is good when the impedance values recorded by the electrodeinitially decrease and then plateau.

A method for predicting lesion quality may include: injecting animpedance-modifying agent into a pulmonary vein from a medical device,the medical device including an occlusion element at least partiallyoccluding the pulmonary vein and a distal electrode positioned withinthe pulmonary vein; recording a plurality of impedance values by theelectrode within the pulmonary vein over a period of time afterinjection of the impedance-modifying agent into the pulmonary vein, theimpedance-modifying agent one of increasing impedance within thepulmonary vein and decreasing impedance within the pulmonary vein;calculating a change in impedance values over the period of time;determining a pulmonary vein occlusion status based at least in part onthe change in impedance values over the period of time, the pulmonaryvein occlusion status being one of: complete occlusion when theimpedance-modifying agent increases impedance within the pulmonary veinand the impedance values initially increase and then plateau; incompleteocclusion when the impedance-modifying agent increases impedance withinthe pulmonary vein and the impedance values initially increase and thendecrease; complete occlusion when the impedance-modifying agentdecreases impedance within the pulmonary vein and the impedance valuesinitially decrease and then plateau; and incomplete occlusion when theimpedance-modifying agent decreases impedance within the pulmonary veinand the impedance values initially decrease and then increase. Themethod may further include assessing the quality of an occlusion of thepulmonary vein by the medical device based on the determined pulmonaryvein occlusion status; and at least one of: repositioning the medicaldevice when the pulmonary vein occlusion status is determined to beincomplete occlusion; and ablating tissue surrounding the pulmonary veinwith the occlusion element when the pulmonary vein occlusion status isdetermined to be complete occlusion.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and theattendant advantages and features thereof, will be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1 shows an exemplary system for the assessment of pulmonary veinocclusion;

FIG. 2 shows a close-up view of a distal end of a medical device of thesystem in FIG. 1;

FIG. 3 shows an exemplary placement of the medical device of FIG. 2proximate a pulmonary vein;

FIG. 4A shows a distal portion of a medical device completely occludinga pulmonary vein;

FIG. 4B shows a distal portion of a medical device partially occluding apulmonary vein;

FIG. 5A shows a graphical representation of changes in impedance when acontrast with impedance-increasing agent is injected into a pulmonaryvein;

FIG. 5B shows a graphical representation of changes in impedance when acontrast with impedance-decreasing agent is injected into a pulmonaryvein;

FIGS. 6A-6C show exemplary charts of data for the assessment ofpulmonary vein occlusion based on impedance when an impedance-decreasingagent is injected into a pulmonary vein;

FIGS. 7A-7D show exemplary charts of data for the assessment ofpulmonary vein occlusion based on impedance; and

FIGS. 8A-8C show exemplary charts of data showing cryoablation qualitybased on a pre-assessed occlusion by temperature.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to FIGS. 1 and 2, an exemplary system for the assessmentof pulmonary vein occlusion is shown. The system 10 may generallyinclude a treatment device 12, such as a cryotreatment catheter, forthermally treating an area of tissue and a console 14 that housesvarious system 10 controls. The system 10 may be adapted for acryotreatment procedure, such as cryoablation. The system 10 mayadditionally be adapted for radiofrequency (RF) ablation and/or phasedRF ablation, ultrasound ablation, laser ablation, microwave ablation,hot balloon ablation, or other ablation methods or combinations thereof.The system 10 may also include a mapping catheter 16 for sensing andrecording electrical signals from tissue (for example, cardiac tissueand/or tissue within a pulmonary vein).

The treatment catheter 12 may generally include a handle 18, an elongatebody 20 having a distal portion 22 and a proximal portion 24, one ormore treatment elements 26, a shaft 28, an electrode 30 distal to theone or more treatment elements 26, and a longitudinal axis 32. Theelectrode 30 may be configured to measure both impedance andtemperature. As a non-limiting example, the electrode 30 may be a 0.5 mmring thermocouple electrode that functions as a thermocouple forrecording temperature data and an electrode for delivering energy and/orrecording impedance and/or other mapping data. Alternatively, theelectrode 30 may measure impedance only and the treatment catheter 12may additionally include one or more thermocouples or other temperaturesensors 33. For example, the treatment catheter 12 may include one ormore thermocouples 33 proximate (either distal to or proximal to) theelectrode 30 (for example, as shown in FIG. 2). In either configuration,the treatment catheter 12 may also include a thermocouple or othertemperature sensor 33A within the treatment element 26. Further, thetreatment catheter 12 may include a reference electrode 34. Thetreatment element 26 may be a balloon, as shown in FIGS. 1-3, and mayalso function as an occlusion element. The balloon 26 may be coupled tothe distal portion 22 of the elongate body 20 of the treatment catheter12. For example, the balloon 26 may define a proximal portion or neck 36that is affixed to or coupled to the distal portion 22 of the elongatebody 20, and may further define a distal portion or neck 38 that isaffixed to or coupled to the shaft 28 (such as the distal portion 40 ofthe shaft 28). The electrode 30 and/or one or more thermocouples 33 maybe positioned just distal to the distal neck 38 of the balloon 26.However, it will be understood that the balloon 26 may be coupled,affixed, disposed on, integrated with, or otherwise attached to theelongate body 20 and/or the shaft 28. Additionally, multiple balloonsmay be used, such as when the balloon 26 is disposed within or without asecond balloon (not shown). The shaft 28 may lie along the longitudinalaxis 32 and be longitudinally movable within the elongate body 20. Inthis manner, longitudinal movement of the shaft 28 will affect the shapeof the balloon 26. The proximal portion of the shaft 28 may be inmechanical communication with one or more steering mechanisms 41 in thehandle 18 of the treatment catheter 12, such that the shaft 28 may belongitudinally extended or retracted using one or more steeringmechanisms 41, such as knobs, levers, wheels, pull cords, and the like.The shaft 28 may include a central lumen 42 and an opening in the distalend of the shaft for delivering fluid, such as a mixture of a contrastmedium and an impedance-modifying agent, into the patient's body (forexample, the pulmonary vein).

In addition to the shaft 28, the treatment catheter 12 may include oneor more lumens, such as a fluid injection lumen 43 and a fluid recoverylumen, for circulating coolant through from a fluid reservoir (which maybe part of, disposed within, and/or in communication with the console14) through the elongate body and to the balloon 26, and for recoveringexpended coolant from the balloon 26 and collecting the expended coolantwithin a fluid reservoir or venting to the atmosphere. Further, thetreatment catheter 12 may include a fluid delivery element 44 that is influid communication with the fluid injection lumen 43. As a non-limitingexample, the fluid delivery element 44 may be wound about at least aportion of the shaft 28 within the balloon 26, as shown in FIG. 1. Thefluid delivery element 44 may be configured to direct a spray of coolanttoward the distal portion of the balloon 26. The fluid delivery element44 may direct coolant in a direction that is substantially orthogonal(that is, approximately 90°) (as shown in FIG. 1) to the longitudinalaxis 32 or in a direction that is at an angle that is less than 90° tothe longitudinal axis 32. For example, the fluid delivery element 44 mayinclude a plurality of outlet ports 45 that are configured to deliverfluid at an angle α from the longitudinal axis 32 of the device, such asat an angle α of between approximately 30° and approximately 45° (±5°)(as shown in FIG. 2). However, it will be understood that the fluiddelivery element 44 may have any configuration that is suitable fordirecting fluid toward the distal portion of the balloon 26. If thetreatment catheter 12 includes thermoelectric cooling elements orelectrodes capable of transmitting radiofrequency (RF), ultrasound,microwave, electroporation energy, or the like, the elongate body 20 mayinclude a lumen in electrical communication with an energy generator(which may be part of, disposed within, and/or in communication with theconsole 14).

The mapping catheter 16 may be passable (longitudinally movable) throughthe shaft 28. The mapping catheter 16 may include one or more pairs ofmapping elements 46, such as electrodes capable of sensing and recordingelectrograms from cardiac tissue. The one or more pairs of mappingelements 46 may be composed of metal or other electrically conductivematerial and may be affixed on an outer surface of the mapping catheter16, integrated and flush with the body of the mapping catheter 16 (suchthat the mapping catheter has a smooth outer surface), may be areas ofexposed electrically conductive material (for example, where an outerinsulative layer has been removed), or may be otherwise affixed, coupledto, or integrated with the mapping catheter 16. The mapping catheter 16may be in deformable and/or steerable using one or more steeringmechanisms 41 into a variety of configurations. For example, the distalof the mapping catheter 16 may be deformable into a lasso-typeconfiguration, such that the loop portion 48 and mapping elements 46 maybe in contact with at least a portion of an inner circumference of a PV.

The console 14 may be in electrical and fluid communication with thetreatment catheter 12 and the mapping catheter 16, and may include oneor more fluid (for example, cryotreatment coolant) reservoirs, includingan impedance-modifying agent reservoir 49, one or more coolant recoveryand/or source reservoirs 50, energy generators 51, and computers 52 withdisplays 54, and may further include various other displays, screens,user input controls, keyboards, buttons, valves, conduits, connectors,power sources, processors, and computers for adjusting and monitoringsystem 10 parameters. The one or more coolant recovery and/or sourcereservoirs 50 may be in fluid communication with the balloon 26 and theimpedance-modifying agent reservoir 49 may be in fluid communicationwith the central lumen 42 and distal opening 55 of the shaft 28. As usedherein, the term “computer” may refer to any programmabledata-processing unit, including a smart phone, dedicated internalcircuitry, user control device, or the like. The computer 52 may includeone or more processors 56 that are in electrical communication with theone or more pairs of mapping elements 46, the electrode 30, the one ormore thermocouples 33, 33A, the one or more treatment elements 26,and/or one or more valves and programmable to execute an algorithm forlocating one or more optimal treatment areas, for controlling thetemperature of the one or more treatment elements 26, for generating oneor more displays or alerts to notify the user of various system criteriaor determinations, and/or for predicting temperature within targettissue based at least in part on signals from the electrode 30 and/orone or more other temperature sensors 33, 33A. As a non-limitingembodiment, the proximal portion of the mapping catheter 16 may includean electrical connection that is mateable to at least a portion of theconsole (for example, with the electrophysiology recording equipment)and in electrical communication with the one or more processors 56.Additionally, the electrode 30 may be in electrical communication withan energy generator 51 for the application of energy to the electrode 30for sensing impedance and, optionally, for mapping cardiac electrogramsfrom adjacent tissue and/or thermally treating tissue. Furthermore,electrodes 30 and 34 may be used for 3D navigation of the treatmentcatheter 12 within the atrial chamber and positioning the treatmentcatheter 12 within, for example, a pulmonary vein. This may allow theoperator to avoid placing the one or more treatment elements 26 too deepwithin the pulmonary vein, and may enable the operator to avoidextracardiac tissues and again navigate the one or more treatmentelements 26 into the pulmonary vein if repeated ablation is needed.Additionally, marking the position of the one or more treatment elements26 may allow the operator to mark the ablated pulmonary veins ifmultiple pulmonary vein branches and common ostium is present.

The console 14 may also include one or more valves that are inelectrical and/or mechanical communication with, and controllable by,the console 14. For example, the computer 52 and/or one or moreprocessors 56 may be programmable to control various system components,such as the one or more valves, to operate according to a duty cyclethat includes opening and closing the one or more valves to regulate theflow of coolant through the system 10 and the treatment catheter 12, andto thereby regulate the temperature of the treatment element 26 (forexample, the balloon 26). The duty cycle may be programmable by the userand/or may be automatically set by the console 14 according to apredicted tissue temperature based at least in part on signals from theelectrode 30, mapping elements 46, and/or temperature sensors 33, 33A.

Referring now to FIG. 2, a close-up view of the distal portion of afirst embodiment of the balloon catheter is shown. As shown anddescribed in FIG. 1, the treatment catheter 12 may include a distalelectrode 30. The treatment catheter 12 may further include a referenceelectrode 34 and one or more thermocouples or other temperature sensors33 if the electrode 30 is not configured to measure temperature. Theelectrodes 30 and 34 may be composed of an electrically conductivematerial suitable for sensing impedance and, optionally, temperature. Asshown in FIGS. 1 and 2, the electrode 30 (and a thermocouple ortemperature sensor 33, if included in the device) may be located distalto the balloon 26. The electrode 30 may be coupled to, affixed to,disposed about, integrated with, or otherwise located on a distalportion of the treatment catheter 12. The electrode 30 and/or one ormore thermocouples 33 may be located immediately distal to the balloon26, such as on the shaft distal portion 40. For example, the electrode30 may be adjacent to or abut the distal end of the balloon 26. Thereference electrode 34 may be located proximal to the balloon 26, suchas on the elongate body distal portion 22. As a non-limiting example,the balloon 26 may have a diameter of approximately 23 mm toapproximately 28 mm.

Referring now to FIG. 3, a treatment catheter is shown positionedproximate a pulmonary vein ostium for a pulmonary vein ablationprocedure (which may also be referred to as a pulmonary vein isolation(PVI) procedure). As used herein, the term “PV tissue” or “pulmonaryvein tissue” may include tissue of the PV ostium, the PV antrum, LA walltissue, and/or tissue at the junction between the LA and PV, and is notlimited to tissue within the PV. In fact, ablation of tissue within thePV may be undesirable. The inflated balloon 26 may be positioned at thepulmonary vein (PV) ostium to occlude the PV, or block the flow of bloodfrom the PV into the left atrium (LA) of the heart. Occlusion of the PVnot only serves to position the balloon 26 to create a circumferentiallesion around the PV ostium, but also prevents warm blood from flowingover the portions of the balloon 26 that are in contact with the targettissue, thereby enhancing the ability of the balloon 26 to reachsufficiently cold temperatures for creating permanent, andcircumferential, cryoablation lesions on or in the target tissue. If thePV is not completely occluded, blood flow past the balloon 26 may havethe effect of raising the temperature of the balloon 26, possiblyresulting in the formation of reversible lesions on or in the targettissue. The blocked blood within the PV may be referred to as “stagnant”blood, whereas the blood within the LA may be referred to as “flowing”blood, as blood may still enter the LA from the other three PVs that arenot being occluded by the treatment catheter 12.

As shown in FIG. 3, the balloon 26 may be positioned at the PV ostiumsuch that the shaft distal portion 40, including the electrode 30 and/orone or more thermocouples 33, is disposed within the PV, within thestagnant blood. An injection of an impedance-modifying agent only or amixture of a biocompatible contrast medium and an impedance-modifyingagent may be introduced into the PV at a fixed rate, volume, andtemperature. As a non-limiting example, the contrast medium/agentmixture may be expelled in an amount of approximately eight cc and at apressure of approximately 125±12 PSI.

As noted above, an agent may be used that alters the conductivity of theblood within the pulmonary vein when injected from the treatmentcatheter 12 into the pulmonary vein and mixes with the blood. Forexample, the agent may be, for example, sterile water, deionized water,iodine solution (diluted in saline 50%), distilled water, or hypertonicsaline with typical boluses of up to 10 cc injected from the device.Although the agent may be injected in a fluid mixture referred to hereinas a “contrast medium/agent mixture,” it will be understood that theagent alone may be used when mixed with contrast medium. However, itwill be understood that any agent or contrast medium/agent mixture willbe injected into the patient's body in small enough amounts to avoidinterfering with the blood's normal ionic balance and negativelyaffecting body function. Further, the agent may be used alone withoutcontrast medium if the patient is intolerant to contrast medium, such asdue to an allergy or kidney problems, or if it is desired to reduce oreliminate the use of fluoroscopy.

The agent may adjust the conductivity (and therefore impedance) of bloodby either increasing blood conductivity (for example, if a hypertonicsolution is used) or decreasing blood conductivity (for example, ifdistilled water, sterile water, or deionized water is used). An agentthat increases blood conductivity may lead to a decrease in impedancewithin the PV as measured by the treatment catheter 12 as the contrastmedium/agent mixture is injected into the PV (for example, from theopening in the distal end of the shaft 28). If the balloon 26 iscompletely occluding the PV (as shown in FIG. 4A), the local impedancewithin the PV may remain low for a longer period. If, on the other hand,the balloon 26 is partially or incompletely occluding the PV (as shownin FIG. 4B), the contrast medium/agent mixture may leak past the balloon26 out of the PV and into the left atrium. In that case, a decrease inlocal impedance will not be as significant and will remain for a shorterperiod of time until all of the contrast medium/agent mixture has flowedfrom the PV into the left atrium. These trends in impedance value changeare shown in FIG. 5A. In FIG. 5A, a mixture of contrast medium and anagent that increases conductivity may be injected into the pulmonaryvein and impedance values recorded by the electrode 30. During Phase I,the impedance will initially decrease. If the PV is completely occluded,the impedance will remain low during Phase II (that is, the valuesplateau). If, on the other hand, the PV is less than completelyoccluded, the impedance will increase during Phase II.

Conversely, an agent that decreases blood conductivity may lead to anincrease in impedance within the PV as measured by the treatmentcatheter 12 as the contrast medium/agent mixture is injected into the PV(for example, from the opening in the distal end of the shaft 28). Asmall leak around the balloon 26 may not produce as great an impedancechange (that is, it may produce a change having a lower peak for ashorter period of time), whereas complete occlusion (an absence of aleak) may result in impedance within the PV may produce a change havinga higher peak for a longer period of time (that is, an impedance curvehaving a bigger crest and a larger surface area under the curve). Thesetrends in impedance value change are shown in FIG. 5B. In FIG. 5B, amixture of contrast medium and an agent that decreases conductivity maybe injected into the pulmonary vein and impedance values recorded by theelectrode 30. During Phase I, the impedance will initially increase. Ifthe PV is completely occluded, the impedance will remain high duringPhase II (that is, the values plateau). If, on the other hand, the PV isless than completely occluded, the impedance will decrease more rapidlyduring Phase II in proportion to the leak rate.

FIGS. 6A-6C show impedance curves for fair occlusion, good occlusion,and poor occlusion, respectively, using only sterile water, whichdecreases blood conductivity. FIGS. 6A-6C show impedance curves overPhase II, or impedance changes after the injection of the agent.Although the data shown in FIGS. 6A-6C was obtained by injecting agentonly (sterile water), it will be understood that a contrast medium/agentmixture may be used instead. In FIG. 6A, the presence of a leak isindicated by the low impedance values. In FIG. 6B, good occlusion isindicated by the relatively higher impedance values.

Continuous impedance and temperature measurements may be taken duringdevice placement and ablation by the electrode 30 and/or mappingelements 46 of the mapping catheter 16 and the measurements may be usedto determine whether the PV is completely occluded. As discussed above,changes in impedance after injection of a contrast medium/agent mixtureinto the PV may be monitored to evaluate PV occlusion quality. Further,if changes in impedance indicate that the PV is less than completelyoccluded, the rate of impedance change (that is, as the contrastmedium/agent mixture leaks into the left atrium) may be correlated tothe degree of occlusion. For example, a higher peak and small rate ofchange may indicate that a small leak is present, whereas a smaller peakand greater rate of change may indicate that a larger leak is present.Complete occlusion may suggest that a permanent lesion will be formed asa result of the ablation procedure.

If impedance measurements indicate that the PV is not permanentlyablated and/or less than fully occluded, the treatment catheter 12 maybe repositioned until complete PV occlusion is indicated by evaluationof the impedance temperature measurements. For example, the one or moreprocessors 56 of the console computer 52 may be programmed to receiveand process data from the one or more electrodes and/or thermocouples,and to generate an alert to the user indicating that the device shouldbe repositioned to achieve complete PV occlusion or that the device isalready optimally positioned.

In addition to impedance measurements, a visual evaluation may also beused to assess PV occlusion. For example, fluoroscopic imaging may beused to visually evaluate the time it takes for the contrastmedium/agent mixture to dissipate from the area of the PV proximate thetreatment catheter 12. Further, visual evaluation may be used inaddition to temperature measurements. Generally, if the PV is completelyoccluded by the treatment element 26, it will take longer for thecontrast medium/agent mixture (which may appear as being darker than thesurrounding blood under fluoroscopic imaging) to dissipate from the areaproximate the treatment catheter 12. In contrast, if PV occlusion ispoor, the contrast medium/agent mixture may quickly dissipate with thenormal direction of blood flow, such as from the pulmonary vein into theleft atrium of the heart.

After PV occlusion assessment, which may be conducted prior to thermallytreating target tissue, the balloon 26 may then be cooled to atemperature sufficient to ablate tissue and applied to the tissuesurrounding the PV opening (for example, the PV ostium and/or the PVantrum). Once the balloon 26 has reached ablation temperature, thetemperature sensed by the electrode 30 or the thermocouple positioneddistal to the balloon 26 and within the PV and a temperature sensedwithin the balloon may be compared for each of the occlusion ratings(i.e. good occlusion, fair occlusion, and poor occlusion). Thethermocouple or other temperature sensor 33A may be located within theballoon 26.

Similar to FIGS. 6A and 6B, FIGS. 7A-7D show assessment of PV occlusionbased on impedance sensed by the distal electrode 30. FIG. 7A showsimpedance curves over time for five discrete tests and an averageimpedance curve over time for an occlusion that is considered to be agood occlusion using an contrast medium/agent mixture that decreasesconductivity (for example, a non-ionic contrast medium/saline mixture).FIGS. 7A-7D show impedance curves over Phase II, or impedance changesafter the injection of the contrast medium/agent mixture. Although thedata shown in FIGS. 7A-7D was obtained by injecting a contrastmedium/agent mixture, it will be understood that only an agent may beused instead. FIG. 7B shows impedance curves over time for sevendiscrete tests, an average impedance curve over time, and a baselineimpedance curve for an occlusion that is considered to be a fairocclusion. FIG. 7C shows impedance curves over time for eight discretetests, an average impedance curve over time, and a baseline impedancecurve for an occlusion that is considered to be a poor occlusion. FIG.7D shows exemplary average impedance curves over time for each ofocclusions that are considered to be good (referred to as “Rating 3” inFIG. 7D), fair (referred to as “Rating 2” in FIG. 7D), and poor(referred to as “Rating 1” in FIG. 7D) occlusions.

FIGS. 8A-8I show cryoablation quality based on a pre-assessed occlusionby temperature measurements. For example, FIG. 8A shows temperaturecurves over time as measured by a thermocouple 33A within the balloon 26for two discrete tests, the data indicating that cryoablation quality ishigh as a result of what is considered to be a good occlusion. FIG. 8Btemperature curves over time as measured by a thermocouple 33A withinthe balloon 26 for five discrete testes, the data indicating that thecryoablation quality is fair as a result of what is considered to be afair occlusion. FIG. 8C shows exemplary average temperature curves overtime as measured by a thermocouple 33A within the balloon 26 for each ofocclusions that are considered to be good (referred to as “Rating 3” inFIG. 8C), fair (referred to as “Rating 2” in FIG. 8C), and poor(referred to as “Rating 1” in FIG. 8C). Temperature data

Using data received by the electrodes 30 and, optionally, the one ormore thermocouples 33, 33A, the occlusion can be qualified as good,fair, or poor by the one or more processors 56. For example, the one ormore processors 56 may receive and process data from the treatmentcatheter 12 and the mapping device 16, and may use the data to calculaterates of impedance change over time (ΔI/Δt) and determine or assign anocclusion status based on the impedance-modifying effects of thecontrast medium/agent mixture or agent alone. That is, whether the agent(alone or mixed with a contrast medium) increases or decreases bloodimpedance will be considered by the one or more processors 56 in makingan occlusion status determination, as discussed above. Additionally, theone or more processors 56 may use the occlusion status determination topredict lesion quality, based on the phenomenon that good occlusion willresult in good lesion quality. The one or more processors 56 may furthercommunicate determinations and/or the calculations to the user via theone or more displays 54. Additionally or alternatively, the system 10may communicate results to the user via one or more visual or audioalerts. Occlusion assessment determinations may be displayed to the usergraphically in a manner that is quickly understood. As a non-limitingexample, a colored graphical element may be displayed, with the colorgreen indicating good PV occlusion, the color yellow indicating fair PVocclusion, and the color red indicating poor PV occlusion.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings without departing from the scope andspirit of the invention, which is limited only by the following claims

What is claimed is:
 1. A medical system comprising: a treatment deviceincluding: a balloon; an electrode located distal to the balloon, theelectrode being configured to record impedance measurements; and atemperature sensor located distal to the balloon, the temperature sensorbeing configured to record temperature measurements; a coolantreservoir, the coolant reservoir containing a coolant and being in fluidcommunication with the balloon; and an impedance-modifying agentreservoir, the impedance-modifying agent reservoir containing animpedance-modifying agent and being in fluid communication with thetreatment device and fluidly isolated from the coolant reservoir.
 2. Themedical system of claim 1, further comprising a processor, the processorbeing programmed to determine a position of the balloon relative to anarea of tissue based on at least one of impedance measurements receivedfrom the electrode and temperature measurements received from thetemperature sensor.
 3. The medical system of claim 2, wherein the areaof tissue is an ostium of a pulmonary vein, the processor being furtherprogrammed to: receive impedance data from the electrode, the impedancedata being recorded by the electrode before, during, and after adelivery of the impedance-modifying agent from the treatment device to alocation within the pulmonary vein; calculate an impedance change overtime; and determine an occlusion status of the ostium of the pulmonaryvein by the balloon based on the calculated impedance change over time.4. The medical system of claim 3, wherein the impedance data is recordedby the electrode continuously before, during, and after the delivery ofthe impedance-modifying agent from the treatment device to a locationwithin the pulmonary vein.
 5. The medical system of claim 3, wherein theimpedance-modifying agent increases an impedance of fluid within thepulmonary vein.
 6. The medical system of claim 5, wherein the processoris programmed to determine the occlusion status is poor when theimpedance change over time indicates an initial impedance increase andthen an impedance decrease over time.
 7. The medical system of claim 5,wherein the processor is programmed to determine the occlusion status isgood when the impedance change over time indicates an initial impedanceincrease and then an impedance plateau.
 8. The medical system of claim3, wherein the impedance-modifying agent decreases an impedance of fluidwithin the pulmonary vein.
 9. The medical system of claim 8, wherein theprocessor is programmed to determine the occlusion status is poor whenthe impedance change over time indicates an initial impedance decreaseand then an impedance increase over time.
 10. The medical system ofclaim 8, wherein the processor is programmed to determine the occlusionstatus is good when the impedance change over time indicates an initialimpedance decrease and then an impedance plateau.
 11. The medical systemof claim 2, wherein the processor is further programmed to predict aquality of an ablation lesion created in the area of tissue by theballoon based on the position determination.
 12. The medical system ofclaim 1, wherein the temperature sensor is a first temperature sensor,the treatment device further including a second temperature sensorwithin the balloon.
 13. The medical system of claim 1, wherein thetreatment device further includes a shaft having a central lumen and adistal opening, the shaft being at least partially disposed within theballoon, the central lumen and distal opening being in fluidcommunication with the impedance-modifying agent reservoir.
 14. Themedical system of claim 1, wherein the impedance-modifying agent is amixture of a contrast medium and an impedance-modifying fluid.
 15. Asystem for predicting lesion quality, the system comprising: a treatmentdevice including: an elongate body having a proximal portion, a distalportion, and a lumen therebetween; an occlusion element coupled to thedistal portion of the elongate body; an electrode located distal to theocclusion element, the electrode being configured to record impedancevalues; and a shaft located within the lumen of the elongate body andhaving a fluid injection lumen, the occlusion element being coupled toat least a portion of the shaft; a fluid reservoir containing animpedance-modifying fluid, the fluid reservoir being in fluidcommunication with the fluid injection lumen of the shaft and the shaftbeing configured to deliver the impedance-modifying fluid into apulmonary vein; and a processor in communication with and receivingimpedance values from the electrode, the processor programmed to:determine an impedance at a first time point, the first time point beinga delivery of impedance-modifying fluid into the pulmonary vein by thetreatment device; calculate a rate of impedance change over time fromthe first time point; and determine a pulmonary vein occlusion statusbased at least in part on the rate of impedance change over time fromthe first time point.
 16. The system of claim 15, wherein theimpedance-modifying fluid is a mixture of an impedance-modifying agentand a contrast medium.
 17. The system of claim 15, wherein theimpedance-modifying fluid one of increases an impedance of a fluidwithin the pulmonary vein and decreases the impedance of the fluidwithin the pulmonary vein, the processor being programmed to: when theimpedance-modifying fluid increases the impedance of the fluid withinthe pulmonary vein, determine the pulmonary vein occlusion status ispoor when the impedance values recorded by the electrode initiallyincrease and then decrease over time, and the processor is programmed todetermine the pulmonary vein occlusion status is good when the impedancevalues recorded by the electrode initially increase and then plateau;and when the impedance-modifying fluid decreases the impedance of thefluid within the pulmonary vein, determine the pulmonary vein occlusionstatus is poor when the impedance values recorded by the electrodeinitially decrease and then increase over time, and the processor isprogrammed to determine the pulmonary vein occlusion status is good whenthe impedance values recorded by the electrode initially decrease andthen plateau.
 18. A method for predicting lesion quality, the methodincluding: injecting an impedance-modifying fluid into a pulmonary veinfrom a medical device, the medical device including an occlusion elementat least partially occluding the pulmonary vein and a distal electrodepositioned within the pulmonary vein; recording a plurality of impedancevalues by the distal electrode within the pulmonary vein over a periodof time after injection of the impedance-modifying fluid into thepulmonary vein; calculating a change in impedance values over the periodof time; comparing the change in impedance values over the period oftime to a target change in impedance values over time; determining apulmonary vein occlusion status based at least in part on the change inimpedance values over the period of time, the pulmonary vein occlusionstatus being one of complete occlusion and incomplete occlusion; and atleast one of: repositioning the medical device when the pulmonary veinocclusion status is determined to be incomplete occlusion; and ablatingtissue surrounding the pulmonary vein with the occlusion element whenthe pulmonary vein occlusion status is determined to be completeocclusion.
 19. The method of claim 18, wherein the impedance-modifyingfluid is a fluid that increases an impedance of blood within thepulmonary vein and the target change in impedance values over timeincludes an initial increase in impedance values and then a plateau inimpedance values, the method further comprising: determining thepulmonary vein occlusion status is complete occlusion when the change inimpedance values over the period of time is the same as the targetchange in impedance values over time; and determining the pulmonary veinocclusion status is incomplete occlusion when the change in impedancevalues over the period of time is different than the target change inimpedance values over time.
 20. The method of claim 18, wherein theimpedance-modifying fluid is a fluid that decreases an impedance ofblood within the pulmonary vein and the target change in impedancevalues over time includes an initial decrease in impedance values andthen a plateau in impedance values, the method further comprising:determining the pulmonary vein occlusion status is complete occlusionwhen the change in impedance values over the period of time is the sameas the target change in impedance values over time; and determining thepulmonary vein occlusion status is incomplete occlusion when the changein impedance values over the period of time is different than the targetchange in impedance values over time.